Marrow-ablative chemotherapy followed by tandem autologous hematopoietic cell transplantation in pediatric patients with malignant brain tumors.

To improve survival in young children with malignant brain tumors, irradiation-avoiding or -minimizing marrow-ablative chemotherapy (HDCx) with autologous hematopoietic cell transplantation (AuHCT) has been investigated. We evaluated the outcome of 44 children with malignant brain tumors treated with HDCx and tandem AuHCT at Children's Hospital Los Angeles between June 1999 and July 2012. Forty-four children with malignant brain tumors were studied. Twenty-one had medulloblastoma/primitive neuro-ectodermal tumor, eight atypical teratoid/rhabdoid tumor (ATRT), five high-grade glioma, four malignant germ cell tumor, three ependymoma and three choroid plexus carcinoma. Twenty-nine patients received three tandem transplants and 15 received two tandem transplants, respectively. The 5-year PFS and overall survivals (OS) for all patients were 46.3±8.2% and 51.7±8.5%, respectively. The PFS and OS for 27 newly diagnosed patients were 68.9±9.9% and 73.5±9.3%, respectively, compared with 17 transplanted at relapse 11.8±9.8% (P<0.001) and 15.1±12.3% (P=0.0231), respectively. The 5-year PFS and OS in 13 previously unirradiated patients were 74±13% and 74±13% versus 33.2±9.8% and 40.2±10.6% in 31 irradiated patients (P=0.11 and P=0.239), respectively. One patient died of transplant-related toxicity. HDCx with tandem AuHCT is feasible and safe in children with malignant brain tumors with encouraging irradiation-free survival in newly diagnosed children.

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation.

The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B-dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL.

Multicystic peritoneal mesothelioma: a case report.

A case of recurrent cystic peritoneal mesothelioma is reported. Ultrastructurally the tumour cells showed abundant surface microvilli, desmosomes, intracytoplasmic filaments and well-developed basal lamina. The cells demonstrated positive staining for keratin peptides, vimentin and epithelial membrane antigen and, some of them, for carcinoembryonic antigen. No staining was demonstrable for a number of endothelial markers. The findings are in accord with the proposed mesothelial origin of the neoplasm and can be of help in the differential diagnosis of other multicystic neoplasms arising in the peritoneal cavity.